The present invention relates to a pharmaceutical composition comprising a stabilized solid amorphous dispersion, having high drug load, such as 50%-70%, of an extremely low-solubility compound (Compound A) which resulted in significantly enhanced dissolution and bioavailability over the crystalline form of said compound. The compound 4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid (Compound A), as well as methods for making it, is disclosed in U.S. Pat. No. 8,354,444 and WO2011/098398.

4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid (C31H29Cl2F2N3O4) (Compound A) is a potent and selective inhibitor of the p53-MDM2 interaction that activates the p53 pathway and induces cell cycle arrest and/or apoptosis in a variety of tumor types expressing wild-type p53 in vitro and in vivo. Compound A belongs to a novel class of MDM2 inhibitors having potent anti-cancer therapeutic activity, in particular in leukemia such as AML and solid tumors such as for example non-small cell lung, breast and colorectal cancers.
The above-identified international patent application and US Patent describe Compound A in crystalline form and is herein incorporated by reference in its totality. The crystalline form of the compound has an on-set melting point of approximately 277° C. The crystalline forms have relatively low aqueous solubility (<0.05 μg/mL in water) at physiological pHs (which range from pH1.5-8.0) and consequently less than optimal bioavailability (high variability). It is thus desirable to obtain a form of the compound which has improved solubility/dissolution rate and bioavailability.